Status epilepticus (SE) occurs in 45,000 to 65,000 persons annually in the United States and is a medical emergency that requires prompt, effective intervention. Despite the development of effective anticonvulsant therapies, and the recognition that prolonged SE is associated with poor neurological outcome, there is often a significant delay between the onset of SE and successful termination of seizures with conventional treatment. This is due both to the time required for transport of patients to an emergency care facility and, in a significant number of patients, a lack of response to initial anticonvulsant treatment. In 1990, the San Francisco Emergency Medical Services (EMS) system developed a protocol that allowed paramedics to administer intravenous diazepam for the treatment of SE in the field. A preliminary analysis of this protocol suggests that patients who received pre-hospital diazepam therapy had fewer seizures in the emergency department, SE of shorter duration, and were intubated less often than patients in whom conventional anticonvulsant therapy was initiated after hospital arrival. These data indicate that pre-hospital treatment of SE may simplify subsequent management and have a beneficial impact on the clinical course and outcome of patients. Nonetheless, the potential benefits and complications of this treatment strategy have not been assessed in a rigorous manner. This is of particular concern because the respiratory complications of intravenous diazepam may be severe, and reports from EMS systems elsewhere in the U.S. suggest that pre-hospital benzodiazepine therapy of SE is gaining popularity despite the lack of a well designed clinical trial to assess its value. This grant proposal describes a multicenter, prospective, randomized, double-blind study designed to compare the safety and efficacy of intravenous diazepam or lorazepam versus placebo when administered in the field by paramedics to adult patients in SE. The study takes advantage of the highly-centralized San Francisco EMS system which is based at San Francisco General Hospital (SFGH). Paramedics will verify the diagnosis of SEE, administer study drugs, and assess patients during transport while having continual radio contact with an attending physician and Medical Intensive Care Nurse at SFGH. The assessment of patients will include observations of clinical seizure activity, level of consciousness, vital signs, cardiac rhythms, and oxygenation via pulse oximetry. Paramedics will also hook-up an ambulatory EEG recording unit to each study patient at the time of initial contact, and continuous recordings will be maintained throughout the transit and emergency department phase of the study. These recordings will be subsequently interpreted and used to determine the validity of the SE diagnosis by the EMS system. Patients will receive standardized anticonvulsant treatment at the destination hospital, and will be monitored for seizure recurrence, cardiovascular and respiratory complications, need for subsequent intensive care, and neurological condition at discharge. Univariate and multivariate statistical comparisons will be used to determine whether pre-hospital therapy has a significant impact on the management and outcome of patients during transport and subsequent hospitalization.